FcgammaRIV is a mouse IgE receptor that resembles macrophage FcepsilonRI in humans and promotes IgE-induced lung inflammation.
FcgammaRIV is a recently identified mouse activating receptor for IgG2a and IgG2b that is expressed on monocytes, macrophages, and neutrophils; herein it is referred to as mFcgammaRIV. Although little is known about mFcgammaRIV, it has been proposed to be the mouse homolog of human FcgammaRIIIA (hFcgammaRIIIA) because of high sequence homology. Our work, however, has revealed what we believe to be new properties of mFcgammaRIV that endow this receptor with a previously unsuspected biological significance; we have shown that it is a low-affinity IgE receptor for all IgE allotypes. Although mFcgammaRIV functioned as a high-affinity IgG receptor, mFcgammaRIV-bound monomeric IgGs were readily displaced by IgE immune complexes. Engagement of mFcgammaRIV by IgE immune complexes induced bronchoalveolar and peritoneal macrophages to secrete cytokines, suggesting that mFcgammaRIV may be an equivalent of human FceRI(alphagamma), which is expressed by macrophages and neutrophils and especially in atopic individuals, rather than an equivalent of hFcgammaRIIIA, which has no affinity for IgE. Using mice lacking 3 FcgammaRs and 2 FceRs and expressing mFcgammaRIV only, we further demonstrated that mFcgammaRIV promotes IgE-induced lung inflammation. These data lead us to propose a mouse model of IgE-induced lung inflammation in which cooperation exists between mast cells and mFcgammaRIV-expressing lung cells. We therefore suggest that a similar cooperation may occur between mast cells and hFceRI-expressing lung cells in human allergic asthma.
Mancardi
David A
DA
Département d'Immunologie, Unité d'Allergologie Moléculaire et Cellulaire, Paris, France.
Iannascoli
Bruno
B
Hoos
Sylviane
S
England
Patrick
P
Daëron
Marc
M
Bruhns
Pierre
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology*; D007249:Inflammation; D007668:Kidney / Q000166:cytology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG / Q000276:immunology / Q000502:physiology*
C522404:Fcgr4 protein, mouse; C502447:MS4A2 protein, human; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E